Reader TTS

ABSTRACT Attempts to associate methylenetetrahydrofolate reductase (_MTHFR_) gene C677T polymorphism with hypertension have been extensively evaluated, but mostly in Caucasians. We therefore

meta-analysed this polymorphism in association with hypertension and hypertension-in-pregnancy (HIP) among Chinese subjects. A random-effects model was applied irrespective of between-study

heterogeneity, which was evaluated by subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot.

Data on 20 qualified studies totalling 4461 Chinese subjects were meta-analysed. In overall allelic/genotypic models, carriers of 677T or 677TT were consistently at significantly increased

risk of developing hypertension and HIP. No between-study heterogeneity was identified for all genetic models, with the exception for contrast of allele 677T versus 677C in hypertension

association studies (_P_=0.03), and the dominant contrast in HIP association studies (_P_=0.025). Both the subgroup and meta-regression analyses indicated that study design was a potential

source of between-study heterogeneity. Funnel plot and Egger’s test suggested no evidence of publication bias. Taken together, our results supported the notion that carriers of 677T or 677TT

were at significantly increased risk of developing hypertension and HIP, but indicated caution in interpreting this result, because the study design made marginal significant contribution

to the heterogeneity. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution

Subscribe to this journal Receive 12 digital issues and online access to articles $119.00 per year only $9.92 per issue Learn more Buy this article * Purchase on SpringerLink * Instant

access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions *

Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS BMA-BASED MENDELIAN RANDOMIZATION IDENTIFIES BLOOD METABOLITES AS CAUSAL CANDIDATES IN PREGNANCY-INDUCED

HYPERTENSION Article 01 July 2024 HOMOCYSTEINE AND FEMALE FERTILITY, PREGNANCY LOSS AND OFFSPRING BIRTHWEIGHT: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY Article 26 March 2021 EVIDENCE OF A

CASUAL RELATIONSHIP BETWEEN VITAMIN D DEFICIENCY AND HYPERTENSION: A FAMILY-BASED STUDY Article 05 September 2022 REFERENCES * Staessen JA, Wang J, Bianchi G, Birkenhäger WH . Essential

hypertension. _Lancet_ 2003; 361: 1629–1641. Article  Google Scholar  * Niu W, Wu S, Zhang Y, Li W, Ji K, Gao P _et al_. Validation of genetic association in apelin-AGTRL1 system with

hypertension in a larger Han Chinese population. _J Hypertens_ 2010; 28: 1854–1861. Article  CAS  Google Scholar  * Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K . A comprehensive

review of genetic association studies. _Genet Med_ 2002; 4: 45–61. Article  CAS  Google Scholar  * Salanti G, Sanderson S, Higgins JP . Obstacles and opportunities in meta-analysis of

genetic association studies. _Genet Med_ 2005; 7: 13–20. Article  Google Scholar  * Nakata Y, Katsuya T, Takami S, Sato N, Fu Y, Ishikawa K _et al_. Methylenetetrahydrofolate reductase gene

polymorphism: relation to blood pressure and cerebrovascular disease. _Am J Hypertens_ 1998; 11: 1019–1023. Article  CAS  Google Scholar  * Nagy B, Hupuczi P, Papp Z . High frequency of

methylenetetrahydrofolate reductase 677TT genotype in Hungarian HELLP syndrome patients determined by quantitative real-time PCR. _J Hum Hypertens_ 2007; 21: 154–158. Article  CAS  Google

Scholar  * Kobashi G, Yamada H, Asano T, Nagano S, Hata A, Kishi R _et al_. Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia

in Japanese women. _Am J Med Genet_ 2000; 93: 122–125. Article  CAS  Google Scholar  * Niu W, Qi Y, Hou S, Zhai X, Zhou W, Qiu C . Haplotype-based association of the

renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: the Fangshan study. _J Hypertens_ 2009; 27: 1384–1391. Article  CAS  Google Scholar  *

Higgins JP, Thompson SG, Deeks JJ, Altman DG . Measuring inconsistency in meta-analyses. _BMJ_ 2003; 327: 557–560. Article  Google Scholar  * Ioannidis JP, Trikalinos TA . Early extreme

contradictory estimates may appear in published research: the proteus phenomenon in molecular genetics research and randomized trials. _J Clin Epidemiol_ 2005; 58: 543–549. Article  Google

Scholar  * Gao YY, Zhan SY, Yin XJ, Hu YH, Li LM . The relationship between methylenetetrahydrofolate reductase polymorphism and risk of essential hypertension. _J Beijing Med Univ_ 1999;

31: 370–372 [in Chinese]. CAS  Google Scholar  * Wang L, Guo H, Li YM . MTHFR gene C677T polymorphism and variation of plasma homocysteine levels in primary hypertension. _Tianjin Med J_

2002; 30: 579–582 [in Chinese]. CAS  Google Scholar  * Sun XN, Li YM, Guo H . The gene polymorphisms of homocysteine metabolism enzymes and the associated factors in isolated systolic

hypertension. _Chin J Cardiol_ 2003; 31: 269–273 [in Chinese]. Google Scholar  * Li JW, Ye L, Liu J, Li XY . Study on homocysteine metabolism-related enzymes gene polymorphisms in elderly

essential hypertension patients with peripheral arterial occlusive disease. _Chin J Geriatr Care_ 2005; 24: 332–335 [in Chinese]. Google Scholar  * Li XJ, Huang W . The analysis of MTHFR

gene polymorphism in patients with renal damage caused by hypertension and patients with renal parenchymal hypertension. _J Capital Univ Med Sci_ 2006; 27: 497–500 [in Chinese]. Google

Scholar  * Hu RL, Zhao SQ, Niu GM, Zhang CY, Hu RL, Wang ZG _et al_. The association between gene polymorphisms of N5,10-methylene tetrahydrofolate reductase (MTHFR) and Mongol nation

patients with primary hypertension disease and hypertension complicating cerebrovascular disease. _Stroke Nerv Dis_ 2007; 14: 13–15 [in Chinese]. Google Scholar  * Tang Y, Hui C, Wu XY, Luo

JW . The C677T point mutation of N5,10-methylene tetrahydrofolate reductase (MTHFR) and essential hypertension. _Mol Cardiol Chin_ 2007; 7: 205–207 [in Chinese]. Google Scholar  * Xing XR,

Hua Q . Relationships between the polymorphism of methylenetetrahydrofolate reductase gene C677T and hypertension, cardiac structure and function. _Med J Chin PLA_ 2007; 32: 741–744 [in

Chinese]. CAS  Google Scholar  * Lin PT, Cheng CH, Wei JC, Huang YC . Low plasma pyridoxal 5′-phosphate concentration and MTHFR 677C—>T genotypes are associated with increased risk of

hypertension. _Int J Vitam Nutr Res_ 2008; 78: 33–40. Article  CAS  Google Scholar  * Wei SQ, Zheng JH, Shi DW, Zou LH, Bi L . The relationship of MTHFR gene polymorphism with gestational

hypertension and plasma homocysteine levels. _Chin J Mod Med_ 2001; 11: 10–12 [in Chinese]. Google Scholar  * Fu F, Liu H, Liao DL, Xiong LN, He XJ, Zhang W _et al_. Investigation of the

relationship between polymorphism of methylenetetrahydrofolate reductase and pregnancy induced hypertension syndrome. _Jiangxi Med J_ 2003; 38: 401–403 [in Chinese]. Google Scholar  * Li KS,

Wang BY, Chen LM, Mao DW . Detection of methylenetetrahydrofolate reductase gene polymorphism. _Chin J Public Health_ 2004; 20: 762–764 [in Chinese]. CAS  Google Scholar  * Niu XM, Zhang XY

. The relationship between plasma homocysteine metabolism and gestational hypertension. _Chin J Obstet Gynecol_ 2004; 39: 347–348 [in Chinese]. Google Scholar  * Wang HY, Li CM, Wang Z,

Yang F . Relationships between polymorphisms of angiotensin-converting enzyme and methylenetetrahydrofolate reductase genes and genetic susceptibility to pregnancy induced hypertension.

_Chin J Obstet Gynecol_ 2004; 39: 369–372 [in Chinese]. CAS  Google Scholar  * Tian G, She DX, Qi QH . Genetic research between gene polymorphisms of homcysteine metabolism-related enzymes

and preeclampsia. _Chin J Thromb Hemost_ 2005; 11: 197–199 [in Chinese]. Article  Google Scholar  * Wang SM, Shen R, Shi XY, Jiang T, Liu XM, Shi YL _et al_. The relationship between MTHFR

gene polymorphism and gestational hypertension syndrome. _Reprod Contracept_ 2006; 26: 378–379 [in Chinese]. Google Scholar  * Zhang ZH, Zhang RJ, Liu AM, Xu Q, Liu ZH . Study on eNOS gene

and MTHFR gene polymorphisms in preeclampsia. _Chin J Birth Health Hered_ 2007; 15: 21–24 [in Chinese]. Google Scholar  * Ding YS, Guan LX, Wang YH, Zhao L, Chen W . Study on MTHFR and eNOS

gene polymorphisms in pregnancy-induced hypertension in the Hans of Weifang area. _Chin J Birth Health Hered_ 2008; 16: 12–14 [in Chinese]. CAS  Google Scholar  * Wang SM, Wang LG, Liu XJ,

Wu AH, Yu JC, Shi H . Investigation on the association between MTHFR gene C677T polymorphism and preeclampsia. _Chin J Woman Child Health_ 2008; 23: 552–554 [in Chinese]. Google Scholar  *

Shen XN, Huang YP, Tang SH, Zhang CL, Chen WS . The relationship between the polymorphism of MTHFR gene preeclampsia. _J Pract Obstet Gynecol_ 2009; 25: 236–238 [in Chinese]. Google Scholar

  * Kosmas IP, Tatsioni A, Ioannidis JP . Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.

_J Hypertens_ 2004; 22: 1655–1662. Article  CAS  Google Scholar  * Qian X, Lu Z, Tan M, Liu H, Lu D . A meta-analysis of association between C677T polymorphism in the

methylenetetrahydrofolate reductase gene and hypertension. _Eur J Hum Genet_ 2007; 15: 1239–1245. Article  CAS  Google Scholar  * Sohda S, Arinami T, Hamada H, Yamada N, Hamaguchi H, Kubo T

. Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. _J Med Genet_ 1997; 34: 525–526. Article  CAS  Google Scholar  * Boushey CJ, Beresford SA, Omenn GS, Motulsky AG . A

quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. _JAMA_ 1995; 274: 1049–1057. Article  CAS  Google

Scholar  * Ruano-Ravina A, Pérez-Ríos M, Barros-Dios JM . Population-based versus hospital-based controls: are they comparable? _Gac Sanit_ 2008; 22: 609–613. Article  Google Scholar  * Yu

K, Zhang J, Zhang J, Dou C, Gu S, Xie Y _et al_. Methionine synthase A2756G polymorphism and cancer risk: a meta-analysis. _Eur J Hum Genet_ 2010; 18: 370–378. Article  CAS  Google Scholar 

* Pereira TV, Nunes AC, Rudnicki M, Yamada Y, Pereira AC, Krieger JE . Meta-analysis of the association of 4 angiotensinogen polymorphisms with essential hypertension: a role beyond M235T?

_Hypertension_ 2008; 51: 778–783. Article  Google Scholar  * Jie L . _Obstetrics and Gynecology_. Beijing: People’s Medical Publishing House, (1996: 4th; 2000: 5th; 2004: 6th). Download

references ACKNOWLEDGEMENTS This work was supported by the SMC Excellent Young Faculty Award of Shanghai Jiao Tong University (WN), Seed Foundation of Development on Science and Technology

by President of Capital Medical University Affiliated Beijing Anzhen Hospital (2010Z10), Shanghai ‘Chen Guang’ Project (09CG12), the Natural Science Foundation of Shanghai (09ZR1426200), and

the National Science Foundation for Young Scientists of China (Grant Number: 30900808, 81000109). AUTHOR INFORMATION Author notes * W-Q Niu and Y-G You: These authors are joint first

authors. AUTHORS AND AFFILIATIONS * Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong

University School of Medicine, Shanghai, China W-Q Niu * Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Shanghai, China W-Q Niu *

Shanghai Institute of Hypertension, Shanghai, China W-Q Niu * Beijing Tropical Medicine Research Institute, Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China

Y-G You * Department of Epidemiology, Capital Medical University Affiliated Beijing Anzhen Hospital, Beijing Institute of Heart, Lung & Blood Vessel Diseases, Beijing, China Y Qi Authors

* W-Q Niu View author publications You can also search for this author inPubMed Google Scholar * Y-G You View author publications You can also search for this author inPubMed Google Scholar

* Y Qi View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to W-Q Niu or Y Qi. ETHICS DECLARATIONS COMPETING INTERESTS

The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Journal of Human Hypertension website SUPPLEMENTARY INFORMATION

SUPPLEMENTARY FIGURE 1 (PDF 56 KB) SUPPLEMENTARY FIGURE 2 (PDF 61 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Niu, WQ., You, YG. & Qi, Y.

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis. _J Hum Hypertens_ 26, 259–267

(2012). https://doi.org/10.1038/jhh.2011.11 Download citation * Received: 21 December 2010 * Revised: 18 January 2011 * Accepted: 23 January 2011 * Published: 24 February 2011 * Issue Date:

April 2012 * DOI: https://doi.org/10.1038/jhh.2011.11 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable

link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * methylenetetrahydrofolate reductase *

hypertension-in-pregnancy * polymorphism * meta-analysis